Antivirals in pregnancy

As with all influenza viruses, the Pandemic (H1N1) 2009 virus is of particular risk to pregnant women, and especially those in their third trimester. This review looked at research into the safety of the antiviral drugs oseltamivir (Tamiflu) and zanamivir (Relenza) in pregnant and breastfeeding women.

A choice of drug is based on several factors, and prescribers should read this summary alongside advice from the Health Protection Agency. The main findings from this recent Canadian and Japanese research are:

• Both oseltamivir (Tamiflu) and zanamivir (Relenza) are relatively safe for use by pregnant and breastfeeding women, compared to other drugs in pregnancy. Neither drug appears to affect the growth and development of the foetus, however ongoing data collection is important in this area. Only small amounts of oseltamivir and zanamivir are excreted into human milk.
• This research says that oseltamivir appears to be the drug of choice for pregnant women because there is more data on its safety in pregnancy. However, zanamivir can still be used, despite less data being available. The HPA recommend inhaled zanamivir as the preferred drug for use in pregnancy, based on their expert review of the situation and the fact that less of the active drug is absorbed into the blood stream via the inhaled route, which means that there is less chance of the drug crossing into the baby across the placenta.
• If a child is breastfed by a mother on these drugs and the child needs treatment themselves, the recommended dose of oseltamivir or zanamivir should still be given. It should be remembered that current HPA advice on prophylaxis is that antivirals should only be given to children under one year of age when another significant health condition is also present.

Prescribers in the UK (England, Scotland, Wales and Northern Ireland) are advised to follow advice from the Health Protection Agency when prescribing anti-viral medication during pregnancy.

Where was the article published?

This research was carried out by Toshiro Tanaka and colleagues from the Motherisk Program at the Hospital for Sick Children, University of Toronto and the Japan Drug Information Institute in Pregnancy, in Tokyo. The study was published online in the Canadian Medical Association Journal on June 15 2009, and supported by research grants in both countries.

What kind of study was this?

In this review, the researchers carried out a literature search of several databases to locate reports on the use of oseltamivir or zanamivir during pregnancy, lactation and breastfeeding. MEDLINE was searched from 1950 to May 2009, and EMBASE from 1980 to week 19 of 2009. The researchers also collected information from a Japanese information services network on the use of oseltamivir and zanamivir in patients with confirmed influenza. Both drugs were in common use in Japan even before the current pandemic.

What does the research say?

Influenza related complications in pregnancy

The researchers say that little is known about whether influenza viruses are transmitted to the foetus through the placenta, and if the viruses are a cause of malformation in the foetus. However, there is a study which suggests that a high temperature itself is associated with an increased incidence of neural tube defects. Complications from ordinary seasonal influenza are also higher in pregnant women, especially in the third trimester, than in non-pregnant women and in those who have already given birth.

The researchers say that although Pandemic (H1N1) 2009 virus may not be as virulent as anticipated, the increased risk of complications during pregnancy should always be taken into account when caring for affected patients.

Viral transmission in breast milk

It is not known whether influenza viruses can be passed from mother to baby through human milk. However, as human milk is anti-infective for infants, continuing breastfeeding is recommended even if the mother is receiving treatment for Pandemic (H1N1) 2009 virus infection.

Antiviral treatment in pregnancy

Most health agencies advise that drug treatment and chemoprophylaxis be considered, along with other public health measures, for patients at high risk of complications, including pregnant women and infants.

A study showed that oseltamivir was extensively metabolised (broken down) by the placenta. Transfer of the products of oseltamivir across the placenta was incomplete, with minimal accumulation on the foetal side. Other studies have tracked spontaneous miscarriages and malformations after women who were unknowingly pregnant were given the drug. These studies found there to be similar levels of miscarriages and malformations as would be found in the general population. For example, in 90 cases there was one malformation (1.1%), which is within the incidence of major malformations in the general population (1% to 3%).

Zanamivir is inhaled through a dry powder inhaler. The proportion of unchanged drug that reaches the systemic circulation (bioavailability) is 10% to 20% by inhalation, compared to 2% when taken orally. Only four people have been reported as being accidentally exposed to zanamivir while pregnant in clinical trials, therefore the data for this drug is limited.

Antiviral treatment while breastfeeding

One study reports that the maximum milk concentrations of oseltamivir and its active metabolite were such that the infant exposure was calculated at 0.012mg/kg per day, much smaller than the recommended paediatric dose (2 to 4mg/kg per day). The same very small risk of exposure is true for zanamivir when inhaled.

What is the implication and importance of this?

The HPA advise that zanamivir is the preferred drug for pregnant women and has theoretical advantages because of its limited systemic absorption. This means that, as the dose when inhaled is lower than it would be when taken by mouth, there is a chance that the amount circulating in the blood and crossing into the placenta is lower than an equivalent dose of oseltamivir. However, because it is inhaled, respiratory complications also need to be considered, especially in women who are prone to respiratory problems.

Breastfeeding women are advised to take oseltamivir if they require an antiviral. However, if a baby is borne midway through a course of zanamivir, the woman should continue to take that antiviral rather than switching to oseltamivir.